803
positive stools every day although they all seemed normal macroscopically. The twins were only moderately premature, and neither had any risk factor predisposing to N.E.C., except for premature rupture of membranes in the first twin who did not get ill. Both infants showed no significant acidosis. The second twin may have had temporary overfeeding, resulting in regurgitation and delayed gastric emptying. Perhaps this supported the conversion of clostridial spores to toxin-producing invading
bacilli, and N.E.C. developed.3 The first twin did not get N.E.c. even though premature rupof the membranes may have supported growth of anaerobic organisms in the mother’s genital tract. Possibly the antibiotic prophylaxis and the absence of additional risk factors ture
prevented her from becoming ill. Even in otherwise healthy premature infants overfeeding seems to be a considerable risk, especially in the presence of potentially pathogenic bacilli, and it should be avoided. When complications such as diarrhoea, vomiting, abdominal distention, and acidosis develop, cultures of blood and stool are indicated. While blood cultures should be routinely planted in aerobic and anaerobic media, isolation of anaerobes from other specimens should be performed for special purposes only. Department of Pædiatrics, Faculty of Medicine, University of Hamburg, D-2000 Hamburg 20, West Germany
of this observation we are now studying other patients presenting with acute-onset rheumatic disorders.
cance
Rheumatology Unit, Department of Medicine, Royal Postgraduate Medical School, Hammersmith London W12
Hospital,
BARRY BRESNIHAN GRAHAM R. V. HUGHES
REVERSIBLE NEUROPATHY OF VITAMIN-B12 DEFICIENCY WITH NORMAL HÆMOGLOBIN AND
SERUM-VITAMIN-B12 SIR,-A 68-year-old man had had,
at
the age of 43,
gastrectomy because of a peptic ulcer. No vitamin
a
partial
substitution therapy was given, but he took vitamins orally and also received vitamin injections containing traces of vitamin B12’ He was well until 1973 when his mental status deteriorated rapidly. Air encephalography revealed ventricular dilatation, widening of the sulci, and a striking cerebellar atrophy. Serum-vitamin-B12 and Hb were normal, and cerebral atrophy of unknown aetiology was diagnosed. In July, 1976, he was admitted because of increasing muscular weakness and severe dementia. He was bedridden and incontinent of faeces and urine. Laboratory data are shown in the table.
HAEMATOLOGICAL
B12
PICTURE
H. H. HELLWEGE
LYMPHOCYTOTOXIC ANTIBODIES IN STILL’S DISEASE
SiR,--Cold-reactive lymphocytotoxic antibodies (L.C.A.) have been demonstrated in patients with viral illnesses,’ and they may be a marker for viral infection. They have also been detected in other diseases, such as systemic lupus erythematosus,2 which may result from viral infection. Furthermore, serum from 50% of unrelated household contacts of patients with lupus contained L.C.A.3 We have found L.C.A. during the acute onset of adult Still’s disease. A 28-year-old housewife became acutely ill with polyarthritis and high evening fever accompanied by a fleeting macular rash. The erythrocyte-sedimentation rate was 120 mm/h. Tests for rheumatoid factor and antinuclear antibodies were negative. Other investigations were negative, including a routine screening for viral antibodies. 4 weeks after the onset of her symptoms the patient was transferred to this hospital where the characteristic clinical features suggested adult Still’s disease. The course over the subsequent months has been that of a chronic polyarthritis responsive to salicylates and gold. L.C.A. were detected by a modified two-stage microdroplet technique.. Lymphocytes separated by density-gradient centrifugation were incubated with the patient’s serum and a rabbit source of complement for 3t h at 15’C. The serum was tested against the lymphocytes of twenty normal donors. Normal human AB serum, heat-inactivated rabbit serum, and antilymphocyte globulin were included as controls. Cell death was assessed by eosin-dye exclusion. Normal sera caused less than 10% cell death. Serum obtained 1 month after the
onset
of symptoms killed
60% of donor lymphocytes. Serum obtained 2 and 3 months after the onset failed to kill more than 10% of the donor lym-
phocytes. Thus,
serum
from
a
patient
with
acute-onset
adult Still’s
disease contained L.C.A., and these antibodies disappeared 8 weeks after the
onset
of the disease. To
investigate
the
signifi-
1. Mottiroui, V. D., Terasaki, P. I. in Histocompatibility Testing (edited by P.I. Terasaki); p. 301. Baltimore, 1970. 2 Mittal, K. K., Rossen, R. D., Sharp, J. T., Lidsky, M. D., Butler, W. D. Nature, 1970, 225, 1255. 3 De Horatius, R. J., Messner, R. P. J. clin. Invest. 1975, 55, 1254. 4. Terasaki, P. I., McClelland, J. D. Nature, 1964, 204, 998.
factor. Folate determined by Lactobactlitis casei assay. Vitamin by radiotsotope assay. t.F.=mtrtnsic
B12
measured
Neurological signs were consistent with vitamin-B12 neuroVitamin B12 and folic acid were given with rapid improvement of mental symptoms; the neuropathological findings improved more slowly. Although a primary folate deficiency cannot be excluded, the Schilling test demonstrated a defective vitamin B12 absorption probably due to changes after gastrectomy.’ This suggests that our patient had vitamin-B12 deficiency, probably resulting in decreased synthesis of thymidylate synthetase and hence low folate level.2 The serum-vitamin-B,2 recorded may be due to assay error or to pathy.
prior administration of traces of this vitamin. A functional vitamin-B,2 deficiency with ansemia may develop after gastrectomy despite a normal vitamin-B12 value. This may also have been important in the development of our patient’s disorder. Although the haematological and neurological complications of vitamin-B,2 deficiency usually coexist, the neurological abnormality may precede the ansemia by several years.4 The findings in our patient show that the serum-vitamin-BI2 alone cannot be relied on to diagnose the prehaematological vitamin-B12 disorder. We suggest that a Schilling test be done whenever doubts remain as to whether a neuropathy is due to vitamin-B12 deficiency.
the
Medical Department A, Aker Hospital, Oslo 5, Norway 1. 2 3. 4.
Rygvold, O. Scand. J. Gastroent. 1974, suppl. 29, p. 57. Haurani, F. I. Science, 1973, 182, 78. Magnus, E. M. Scand. J. Hœmat. 1975, 24, suppl. p. 80. Jewesburg, E.
C. O. Lancet, 1954, ii, 307.
H. MELSOM S. KORNSTAD U. ABILDGAARD
positive stools every day although they all seemed normal macroscopically. The twins were only moderately premature, and neither had any risk factor predisposing to N.E.C., except for premature rupture of membranes in the first twin who did not get ill. Both infants showed no significant acidosis. The second twin may have had temporary overfeeding, resulting in regurgitation and delayed gastric emptying. Perhaps this supported the conversion of clostridial spores to toxin-producing invading
bacilli, and N.E.C. developed.3 The first twin did not get N.E.c. even though premature rupof the membranes may have supported growth of anaerobic organisms in the mother’s genital tract. Possibly the antibiotic prophylaxis and the absence of additional risk factors ture
prevented her from becoming ill. Even in otherwise healthy premature infants overfeeding seems to be a considerable risk, especially in the presence of potentially pathogenic bacilli, and it should be avoided. When complications such as diarrhoea, vomiting, abdominal distention, and acidosis develop, cultures of blood and stool are indicated. While blood cultures should be routinely planted in aerobic and anaerobic media, isolation of anaerobes from other specimens should be performed for special purposes only. Department of Pædiatrics, Faculty of Medicine, University of Hamburg, D-2000 Hamburg 20, West Germany
of this observation we are now studying other patients presenting with acute-onset rheumatic disorders.
cance
Rheumatology Unit, Department of Medicine, Royal Postgraduate Medical School, Hammersmith London W12
Hospital,
BARRY BRESNIHAN GRAHAM R. V. HUGHES
REVERSIBLE NEUROPATHY OF VITAMIN-B12 DEFICIENCY WITH NORMAL HÆMOGLOBIN AND
SERUM-VITAMIN-B12 SIR,-A 68-year-old man had had,
at
the age of 43,
gastrectomy because of a peptic ulcer. No vitamin
a
partial
substitution therapy was given, but he took vitamins orally and also received vitamin injections containing traces of vitamin B12’ He was well until 1973 when his mental status deteriorated rapidly. Air encephalography revealed ventricular dilatation, widening of the sulci, and a striking cerebellar atrophy. Serum-vitamin-B12 and Hb were normal, and cerebral atrophy of unknown aetiology was diagnosed. In July, 1976, he was admitted because of increasing muscular weakness and severe dementia. He was bedridden and incontinent of faeces and urine. Laboratory data are shown in the table.
HAEMATOLOGICAL
B12
PICTURE
H. H. HELLWEGE
LYMPHOCYTOTOXIC ANTIBODIES IN STILL’S DISEASE
SiR,--Cold-reactive lymphocytotoxic antibodies (L.C.A.) have been demonstrated in patients with viral illnesses,’ and they may be a marker for viral infection. They have also been detected in other diseases, such as systemic lupus erythematosus,2 which may result from viral infection. Furthermore, serum from 50% of unrelated household contacts of patients with lupus contained L.C.A.3 We have found L.C.A. during the acute onset of adult Still’s disease. A 28-year-old housewife became acutely ill with polyarthritis and high evening fever accompanied by a fleeting macular rash. The erythrocyte-sedimentation rate was 120 mm/h. Tests for rheumatoid factor and antinuclear antibodies were negative. Other investigations were negative, including a routine screening for viral antibodies. 4 weeks after the onset of her symptoms the patient was transferred to this hospital where the characteristic clinical features suggested adult Still’s disease. The course over the subsequent months has been that of a chronic polyarthritis responsive to salicylates and gold. L.C.A. were detected by a modified two-stage microdroplet technique.. Lymphocytes separated by density-gradient centrifugation were incubated with the patient’s serum and a rabbit source of complement for 3t h at 15’C. The serum was tested against the lymphocytes of twenty normal donors. Normal human AB serum, heat-inactivated rabbit serum, and antilymphocyte globulin were included as controls. Cell death was assessed by eosin-dye exclusion. Normal sera caused less than 10% cell death. Serum obtained 1 month after the
onset
of symptoms killed
60% of donor lymphocytes. Serum obtained 2 and 3 months after the onset failed to kill more than 10% of the donor lym-
phocytes. Thus,
serum
from
a
patient
with
acute-onset
adult Still’s
disease contained L.C.A., and these antibodies disappeared 8 weeks after the
onset
of the disease. To
investigate
the
signifi-
1. Mottiroui, V. D., Terasaki, P. I. in Histocompatibility Testing (edited by P.I. Terasaki); p. 301. Baltimore, 1970. 2 Mittal, K. K., Rossen, R. D., Sharp, J. T., Lidsky, M. D., Butler, W. D. Nature, 1970, 225, 1255. 3 De Horatius, R. J., Messner, R. P. J. clin. Invest. 1975, 55, 1254. 4. Terasaki, P. I., McClelland, J. D. Nature, 1964, 204, 998.
factor. Folate determined by Lactobactlitis casei assay. Vitamin by radiotsotope assay. t.F.=mtrtnsic
B12
measured
Neurological signs were consistent with vitamin-B12 neuroVitamin B12 and folic acid were given with rapid improvement of mental symptoms; the neuropathological findings improved more slowly. Although a primary folate deficiency cannot be excluded, the Schilling test demonstrated a defective vitamin B12 absorption probably due to changes after gastrectomy.’ This suggests that our patient had vitamin-B12 deficiency, probably resulting in decreased synthesis of thymidylate synthetase and hence low folate level.2 The serum-vitamin-B,2 recorded may be due to assay error or to pathy.
prior administration of traces of this vitamin. A functional vitamin-B,2 deficiency with ansemia may develop after gastrectomy despite a normal vitamin-B12 value. This may also have been important in the development of our patient’s disorder. Although the haematological and neurological complications of vitamin-B,2 deficiency usually coexist, the neurological abnormality may precede the ansemia by several years.4 The findings in our patient show that the serum-vitamin-BI2 alone cannot be relied on to diagnose the prehaematological vitamin-B12 disorder. We suggest that a Schilling test be done whenever doubts remain as to whether a neuropathy is due to vitamin-B12 deficiency.
the
Medical Department A, Aker Hospital, Oslo 5, Norway 1. 2 3. 4.
Rygvold, O. Scand. J. Gastroent. 1974, suppl. 29, p. 57. Haurani, F. I. Science, 1973, 182, 78. Magnus, E. M. Scand. J. Hœmat. 1975, 24, suppl. p. 80. Jewesburg, E.
C. O. Lancet, 1954, ii, 307.
H. MELSOM S. KORNSTAD U. ABILDGAARD
